Fat accumulation around the heart and aorta may impact cardiovascular (CV) health. The purpose of this study was to conduct a systematic investigation to examine potential associations of these fat depots with risk factors for CV events, which has not been done before.

Methods

Pericardial fat, periaortic fat around the ascending aorta (AA), descending aorta (DA) and aortic arch, and abdominal subcutaneous and visceral fat were measured by MRI in older adults with (n=385, 69±8 years, 52% female) and without (n=50, 69±8 years, 58% female) risk factors for a CV event.

Older adults with a high risk for CV events have greater periaortic fat than low-risk adults, even after accounting for BMI. More studies are needed to determine whether greater periaortic fat predicts future CV events.

On average, both exercise interventions significantly improved physical function. For AT, there was a 7.9% increase in VO2peak; individual absolute increases varied from 0.4–4.3 ml/kg/min and four participants (13%) showed no change or a decrease in VO2peak. For RT, knee extensor strength improved an average of 8.1%, but individual increases varied from 1.2–63.7 Nm, and 16 participants (30%) showed no change or a decrease in strength. Majority of participants improved 400-m walk time, usual gait speed, chair rise time, and SPPB with AT, and improved usual gait speed, chair rise time, and SPPB with RT; but, there was wide variation in the magnitude of improvement. Compliance was only related to change in 400-m walk time following RT (r= −0.31; p<0.05).

CONCLUSION

Despite sufficient levels of adherence to both exercise interventions, some participants did not improve function, and the magnitude of improvement varied widely. Additional research is needed to identify factors that optimize responsiveness to exercise to maximize its functional benefits in older adults.

Obesity and visceral adiposity are increasingly recognized risk factors for cardiovascular disease. Visceral fat may reduce myocardial perfusion by impairing vascular endothelial function. Women experience more anginal symptoms compared to men despite less severe coronary artery stenosis, as assessed by angiography. Women and men have different fat storage patterns which may account for the observed differences in cardiovascular disease. Therefore, our objective was to evaluate the relationship between visceral adipose tissue distributions and myocardial perfusion in men and women.

Methods

Visceral and subcutaneous fat distributions and myocardial perfusion were measured in 69 men and women without coronary artery disease using magnetic resonance imaging techniques. Myocardial perfusion index was quantified after first-pass perfusion with gadolinium contrast at peak dose dobutamine stress.

Arterial stiffness is a prominent feature of vascular aging and a risk factor for cardiovascular disease (CVD). Fat around the heart and blood vessels (i.e. pericardial fat, Pfat) may contribute to arterial stiffness via a local paracrine effect of adipose tissue on the surrounding vasculature. Thus, we determined the association between Pfat and carotid stiffness in 5,770 participants (mean age 62 yrs, 53% female, 25% African American, 24% Hispanic, and 13% Chinese) from the Multi-Ethnic Study of Atherosclerosis.

Methods and Results

Pfat was measured by computed tomography, and ultrasonography of the common carotid artery was used to calculate the distensibility coefficient (DC) and young’s modulus (YM). Lower DC and higher YM values indicate stiffer arteries. Pfat quartile was highly associated with demographic, behavioral, anthropometric, hemodynamic, metabolic, and disease variables in both men and women. After adjusting for height, clinical site, CVD risk factors, and medications, a 1-standard deviation (41.91 cm3) increment in Pfat was associated with a 0.00007±0.00002 1/mmHg lower DC (p=0.0002) in men and a 48.1±15.1 mmHg/mm higher YM in women (p=0.002). Additional adjustment for C-reactive protein, coronary artery calcification, and carotid intima-media thickness had only modest effects. More importantly, adjusting for body mass index and waist circumference did not significantly change the overall results.

Elevated circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) have been observed in obese persons and are reduced by weight loss. However, it is not known if combining caloric restriction (CR) with exercise training is better in reducing sLOX-1 levels than CR alone.

The intervention groups were similar at baseline with respect to body weight, body composition, lipids, and blood pressure. However, plasma sLOX-1 levels were higher in the CR only group (99.90 ± 8.23 pg/ml) compared to both the CR + moderate-intensity exercise (69.39 ± 8.23 pg/ml, p=0.01) and CR + vigorous-intensity exercise (72.83 ± 9.36 pg/ml, p=0.03) groups. All three interventions significantly reduced body weight (~14%), body fat, and waist and hip circumferences to a similar degree. These changes were accompanied by a 23% reduction in sLOX-1 levels overall (−19.00 ± 30.08 pg/ml, p<0.0001), which did not differ among intervention groups (p=0.13). Changes in body weight, body fat, and VO2 max were not correlated with changes in sLOX-1 levels. In multiple regression analyses in all women combined, baseline sLOX-1 levels (β = − 0.70 ± 0.06, p<0.0001), age (β = 0.92 ± 0.43, p=0.03) and baseline BMI (β = 1.88 ± 0.66, p=0.006) were independent predictors of the change in sLOX-1 with weight loss.

Conclusions

Weight loss interventions of equal energy deficit have similar effects on sLOX-1 levels in overweight and obese postmenopausal women, with the addition of aerobic exercise having no added benefit when performed in conjunction with CR.

Accumulating evidence suggests that ginkgo biloba is cardioprotective, in part, through its vasodilatory and antihypertensive properties. However, definitive data on its blood pressure-lowering effects in humans is lacking.

At baseline 54% of the study participants were hypertensive, 28% were pre-hypertensive, and 17% were normotensive. Over a median follow-up of 6.1 years, there were similar changes in blood pressure and pulse pressure in the ginkgo biloba and placebo groups. Although baseline hypertension status did not modify the antihypertensive effects of ginkgo biloba, it did influence the changes in blood pressure variables observed during follow-up, with decreases in hypertensives, increases in normotensives, and no changes in pre-hypertensives. Among participants who were not on antihypertensive medications at baseline, there was no difference between treatment groups in medication use over time, as the OR (95% CI) for being a never-user in the ginkgo biloba group was 0.75 (0.48–1.16). The rate of incident hypertension also did not differ between participants assigned to ginkgo biloba vs. placebo (HR, 0.99, 95% CI, 0.84–1.15).

Conclusions

Our data indicate that ginkgo biloba does not reduce blood pressure or the incidence of hypertension in elderly men and women.

Reduced nitric oxide (NO) production and bioactivity is a major contributor to endothelial dysfunction. Animal data suggests that improvements in endothelial function in response to aerobic exercise training may depend on the duration of the training program. However, no studies have examined changes in NO (as assessed by the major NO metabolites, nitrate and nitrite, NOx) after long-term training in humans. In addition, aging may impair the ability of the vasculature to increase NO with exercise. Thus, we determined whether 24 weeks of aerobic exercise training increases plasma NOx levels in sedentary older adults. We also examined changes in forearm blood flow (FBF) at rest and during reactive hyperemia as a measure of vasomotor function. Plasma NOx levels were measured in 82 men and women using a modified Griess assay. FBF was assessed in a subset of individuals (n=15) using venous occlusion plethysmography. After 24 weeks of exercise training, there were significant improvements in maximum oxygen consumption, HDL cholesterol, triglycerides, and body fat. Changes in plasma NOx levels ranged from −14.83 to +16.69 μmol/L; however, the mean change overall was not significant (−0.33±6.30 μmol/L, p=0.64). Changes in plasma NOx levels were not associated with age, gender, race, HDL cholesterol, triglycerides, body weight, body fat, or maximal oxygen consumption. There were also no significant changes in basal FBF, peak FBF, hyperemic response, total hyperemic flow, or minimum forearm vascular resistance with exercise training. In conclusion, improvements in plasma NOx levels and FBF are not evident after long-term training in older adults.

Arterial stiffness is a prominent feature of vascular aging and is strongly related to cardiovascular disease (CVD). Oxidized low-density lipoprotein (ox-LDL), a key player in the pathogenesis of atherosclerosis, may also play a role in arterial stiffening, but this relationship has not been well studied. Thus, we examined the cross-sectional association between ox-LDL and aortic pulse wave velocity (aPWV), a marker of arterial stiffness, in community-dwelling older adults. Plasma ox-LDL levels and aPWV were measured in 2,295 participants (mean age, 74 yrs; 52% female; 40% black) from the Health, Aging and Body Composition study. Mean aPWV significantly increased across tertiles of ox-LDL (tertile 1, 869 ± 376 cm/s; tertile 2, 901 ± 394 cm/s; tertile 3, 938 ± 415 cm/s; p=0.002). In multivariate analyses, ox-LDL remained associated with aPWV after adjustment for demographics and traditional CVD risk factors (p=0.008). After further adjustment for hemoglobin A1c, abdominal visceral fat, anti-hypertensive and antilipemic medications, and CRP the association with ox-LDL was attenuated, but remained significant (p=0.01). Results were similar when ox-LDL was expressed in absolute (mg/dL) or relative amounts (percent of LDL). Moreover, individuals in the highest ox-LDL tertile were 30-55% more likely to have high arterial stiffness, defined as aPWV > 75th percentile (p≤0.02). In conclusion, we found that among elderly persons, elevated plasma ox-LDL levels are associated with higher arterial stiffness, independent of CVD risk factors. These data suggest that ox-LDL may be related to the pathogenesis of arterial stiffness.

Chronic subclinical inflammation may contribute to impaired physical function in older adults; however, more data are needed to determine whether inflammation is a common mechanism for functional decline, independent of disease or health status.

Methods

We examined associations between physical function and inflammatory biomarkers in 542 older men and women enrolled in four clinical studies at Wake Forest University between 2001 and 2006. All participants were at least 55 years and had chronic obstructive pulmonary disease, congestive heart failure, high cardiovascular risk, or self-reported physical disability. Uniform clinical assessments were used across studies, including grip strength; a Short Physical Performance Battery (SPPB; includes balance, 4-m walk, and repeated chair stands); inflammatory biomarker assays for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP); and anthropometric measures.

Results

Higher levels of CRP and IL-6, but not TNF-α, were associated with lower grip strength and SPPB scores and longer times to complete the 4-m walk and repeated chair stands tests, independent of age, gender, and race. More importantly, these relationships were generally independent of disease status. Further adjustment for fat mass, lean mass, or percent body fat altered some of these relationships but did not significantly change the overall results.

Conclusions

Elevated CRP and IL-6 levels are associated with poorer physical function in older adults with various comorbidities, as assessed by a common battery of clinical assessments. Chronic subclinical inflammation may be a marker of functional limitations in older persons across several diseases/health conditions.

The lectin-like ox-LDL receptor 1 (LOX-1) expressed on vascular cells plays a major role in atherogenesis by internalizing and degrading oxidized LDL. LOX-1 can be cleaved from the cell surface and released as soluble LOX-1 (sLOX-1), and elevated sLOX-1 levels may be indicative of atherosclerotic plaque instability. We examined associations between the LOX-1 3′UTR-C/T and G501C polymorphisms and plasma sLOX-1 levels in 97 healthy older men and women. The frequencies for the 3′UTR-T and 501C alleles were 46% and 10%, respectively. Plasma sLOX-1 levels were significantly higher in the 3′UTR CC genotype group compared to both the CT (p=0.02) and TT (p=0.002) genotype groups. Plasma sLOX-1 were also significantly higher in the 501GC genotype group compared to the GG genotype group (p=0.004). In univariate analyses, sLOX-1 levels were significantly associated with both the 3′UTR-C/T and G501 C polymorphisms. These associations remained significant after adjusting for age, gender, race, and BMI. In conclusion, variation in the LOX-1 gene is associated with plasma sLOX-1 levels in older men and women.

Obesity-related increases in multiple inflammatory markers may contribute to the
persistent subclinical inflammation common with advancing age. However, it is unclear if
a specific combination of markers reflects the underlying inflammatory state. We used
factor analysis to identify inflammatory factor(s) and examine their associations with
adiposity in older adults at risk for disability.

IL-2sRα, sTNFRI, and sTNFRII loaded highest on the first factor (factor 1). CRP,
IL-1ra, and IL-6 loaded highest on the second factor (factor 2). Factor 2, but not
factor 1, was positively associated with 1-SD increments in waist
circumference (β = 0.160 ± 0.057, p = .005),
body mass index (β = 0.132 ± 0.053, p = .01),
and total fat mass (β = 0.126 ± 0.053, p =
.02) after adjusting for age, gender, race/ethnicity, site, smoking, anti-inflammatory
medications, comorbidity index, health-related quality of life, and physical function.
These associations remained significant after further adjustment for grip strength, but
only waist circumference remained associated with inflammation after adjusting for total
lean mass. There were no significant interactions between adiposity and muscle mass or
strength for either factor.

Conclusions.

Greater total and abdominal adiposity are associated with higher levels of an
inflammatory factor related to CRP, IL-1ra, and IL-6 in older adults, which may provide
a clinically useful measure of inflammation in this population.

Fat in the renal sinus (RS), a region of the kidney in which low pressure venous and lymphatic vessels are present, may indirectly influence blood pressure (BP). The purpose of this study was to assess the association between RS fat and control of BP upon receipt of antihypertensive medications.

Two hundred-five (205) participants aged 55 to 85 years at risk for cardiovascular (CV) events underwent magnetic resonance imaging assessments of abdominal and RS fat, measurement of blood pressure, and determination of the number of prescribed antihypertensive medications. Multivariable linear regression was used to determine associations between RS fat, blood pressure, and the number of prescribed antihypertensive medications.

In conclusion, after accounting for other body fat depots and risk factors for hypertension, renal sinus fat volume is associated with the number of prescribed antihypertensive medications and stage II hypertension. These results indicate that further studies are warranted to determine if fat accumulation in the renal sinus promotes hypertension.

Persistent, sub-clinical inflammation, as indicated by higher circulating levels of inflammatory mediators, is a prominent risk factor for several chronic diseases, as well as aging-related disability. As such, the inflammatory pathway is a potential therapeutic target for lifestyle interventions designed to reduce disease and disability. Physical exercise is well recognized as an important strategy for reducing the risk of chronic disease, and recent research has focused on its role in the improvement of the inflammatory profile. This review summarizes the evidence for and against the role of increasing physical activity in the reduction of chronic inflammation. Large population-based cohort studies consistently show an inverse association between markers of systemic inflammation and physical activity or fitness status, and data from several small-scale intervention studies support that exercise training diminishes inflammation. However, data from large, randomized, controlled trials designed to definitively test the effects of exercise training on inflammation are limited, and results are inconclusive. Future studies are needed to refine our understanding of the effects of exercise training on systemic low-grade inflammation, the magnitude of such an effect, and the amount of exercise necessary to elicit clinically meaningful changes in the deleterious association between inflammation and disease.

Pericardial fat has adverse effects on the surrounding vasculature. Previous studies suggest that pericardial fat may contribute to myocardial ischemia in symptomatic individuals. However, it is unknown if pericardial fat has similar effects in asymptomatic individuals.

Methods

We determined the association between pericardial fat and myocardial blood flow (MBF) in 214 adults with no prior history of cardiovascular disease from the Minnesota field center of the Multi-Ethnic Study of Atherosclerosis (43% female, 56% Caucasian, 44% Hispanic). Pericardial fat volume was measured by computed tomography. MBF was measured by MRI at rest and during adenosine-induced hyperemia. Myocardial perfusion reserve (PR) was calculated as the ratio of hyperemic to resting MBF.

Results

Gender-stratified analyses revealed significant differences between men and women including less pericardial fat (71.9±31.3 vs. 105.2±57.5 cm3, p<0.0001) and higher resting MBF (1.12±0.23 vs. 0.93±0.19 ml/min/g, p<0.0001), hyperemic MBF (3.49±0.76 vs. 2.65±0.72 ml/min/g, p<0.0001), and PR (3.19±0.78 vs. 2.93±0.89, p = 0.03) in women. Correlations between pericardial fat and clinical and hemodynamic variables were stronger in women. In women only (p = 0.01 for gender interaction) higher pericardial fat was associated with higher resting MBF (p = 0.008). However, this association was attenuated after accounting for body mass index or rate-pressure product. There were no significant associations between pericardial fat and hyperemic MBF or PR after multivariate adjustment in either gender. In logistic regression analyses there was also no association between impaired coronary vasoreactivity, defined as having a PR <2.5, and pericardial fat in men (OR, 1.18; 95% CI, 0.82–1.70) or women (OR, 1.11; 95% CI, 0.68–1.82).

Conclusions

Our data fail to support an independent association between pericardial fat and myocardial perfusion in adults without symptomatic cardiovascular disease. Nevertheless, these findings highlight potentially important differences between asymptomatic and symptomatic individuals with respect to the underlying subclinical disease burden.

Persistent, sub-clinical inflammation predisposes to chronic disease, as well as the development of sarcopenia and disability, in frail elderly. Thus, the inflammatory pathway is a potential target for interventions to reduce aging-related disease and disability. This article highlights emerging data suggesting that increasing physical activity could be effective for reducing chronic inflammation in the elderly.

The purpose of this study was to examine the effects of aerobic exercise training (AEXT) on dipping status in pre-hypertensive and stage-1 hypertensive individuals. A secondary purpose was to evaluate whether AEXT alters oxidative stress and endothelial biomarkers correlated to dipping status.

Before and after AEXT, there were no significant differences between dippers and non-dippers in any of the biomarkers except for total cholesterol following AEXT. In a sub-analysis following AEXT, 14 subjects retained their original dipping status, five subjects changed from dippers to non-dippers and four subjects changed from non-dippers to dippers. Significant differences existed between these groups in changes in total and LDL-cholesterol, ox-LDL, 8-iso-PGF2α and % Dip.

Conclusions

Changes in cholesterol levels but not oxidative stress or endothelial biomarkers were related to changes in BP variables following AEXT in dippers and non-dippers.

Oxidative stress that is mediated through NADPH oxidase activity plays a role in the pathology of hypertension, and aerobic exercise training reduces NADPH oxidase activity. The involvement of genetic variation in the p22phox (CYBA) subunit genes in individual oxidative stress responses to aerobic exercise training has yet to be examined in Pre and Stage 1 hypertensives.

Demographic and subject characteristics were similar among genotype groups for both polymorphisms. At baseline, a significant (P = 0.03) difference among the C2424T genotype groups in 8-iso-PGF2α levels was detected, with the TT homozygotes having the lowest levels and the CC homozygotes having the highest levels. However, no differences were found at baseline between the A640G genotype groups. After 6 months of aerobic exercise training, there was a significant increase in V̇O2max (P < 0.0001) in the entire study population. In addition, there were significant increases in both urinary 8-iso-PGF2α (P = 0.002) and plasma TAC (P = 0.03) levels and a significant decrease in endogenous urinary NOx (P < 0.0001). Overall, aerobic exercise training elicited no significant differences among genotype groups in either CYBA variant for any of the oxidative stress variables.

Conclusions

We found that compared with CYBA polymorphisms C242T and A640G, it was aerobic exercise training that had the greatest influence on the selected biomarkers; furthermore, our results suggest that the C242T CYBA variant influences baseline levels of urinary 8-iso-PGF2α but not the aerobic exercise-induced responses.